ADPKD shows genetic heterogeneity, with at least three different genes implicated: the PKD1 gene (85% of the cases), the PKD2 (15% of the cases), and probably a PDK3 gene not yet identified. Recently, it has been reported that PC1 tail interacts with tuberin, the product of the TSC2 gene. The main function of the tuberin is to inactivate the Ser/Thr kinase mTOR, whose activity has been linked to increased cell growth, proliferation, apoptosis and differentiation. In ADPKD experimental animal models, researchers have shown that cyst lining epithelial cells exhibited very high mTOR activity; thus, they hypothesized that PC1 normally suppresses mTOR activity, and that defects in PC1 (and other proteins) may lead to aberrant mTOR activation. Studies in rat models of ADPKD have shown that short-term treatment with sirolimus (SRL) resulted in the dramatic reduction of the kidney size.